The human immune system has a multitude of natural and adaptive immune mechanisms and reactions for maintaining a healthy state. Immune responses are often divided into humoral and cell-mediated response. Humoral immunity refers broadly to antibody production and actions by B-cells including plasma cells. Cellular immunity is mediated by cells including T-cells, monocytes, macrophages, and histiocytes. T-cells and B-cells are two broad categories of lymphocytes, and T-cells are further categorized according to their various functions or markers, for example as, T-helper (Th) cells or T-suppressor cells. T-helper cells can be divided into different subsets that are distinguished by their cytokine production profiles. Th1 T cell clones produce interleukin-2 (IL-2) and interferon-gamma (IFN-γ), whereas Th2 cell clones secrete IL-10, IL-4, and IL-5. Both classes of Th cell clones produce cytokines such as tumor necrosis factor-alpha (TNF-α), IL-3, and granulocyte-macrophage colony stimulating factor (GM-CSF). A third category of Th cells (Th0) produces IL-2, IFN-γ, IL-4, IL-5, TNF-α, IL-3, and GM-CSF simultaneously.
The different cytokine production patterns of Th1 and Th2 cells reflect their helper functions. Th1 cells are predominantly involved in delayed-type hypersensitivity (DTH) responses, whereas Th2 cells are associated with antibody production. Since antibody (Th2 pathways) and DTH (Th1 pathways) responses are often mutually exclusive, Th1 and Th2 cells are thought to have cross-regulatory effects. IFN-γ produced by Th1 cells inhibits proliferation of Th2 cells, and IL-10 produced by Th2 cells inhibits cytokine synthesis by Th1 cell clones, especially IFN-γ and IL-2 production.
IL-10 is a pluirpotent cytokine with potent effects on various cell populations, in particular circulating and resident immune cells, and thus has broad effects in immunoregulation and host defense. Agents capable of stimulating endogenous production of IL-10 in order to mediate the immune response would be advantageous for therapy of various diseases and conditions.